Introduction: Immunosuppressive therapies used in Inflammatory Bowel Disease (IBD) have been associated with an increased risk of opportunistic infections (OI). While some OIs like Clostridium difficile have been extensively studied, there is limited data on the prevalence of other OIs in a large cohort of unselected IBD patients. The aim of this study was to investigate the epidemiology of OIs in IBD in a large, population-based database. Methods: We performed a retrospective analysis of a large, population based, commercial database (Explorys), that aggregates electronic health records from 26 US healthcare systems. We identified all patients with CD and UC, based on Systemized Nomenclature of Medicine - Clinical Terms from 2013-2018. We compared the prevalence of OIs in this cohort of CD and UC to non-IBD controls. Results: Of the 35,420,110 individuals in the database, we identified 153,290 patients with CD and 128,540 patients with UC. The prevalence of CD and UC was higher in females vs males - (OR [Odds Ratio]; 1.23 for CD; 95% CI 1.22 -1.24 and OR, for UC; 1.17, 95% CI 1.15 - 1.17). When compared to the non-IBD controls, all OIs were more common in CD (OR, 2.87; 95% CI 2.83 - 2.91) and UC (OR, 3.15; 95% CI 3.11 - 3.20). The OI with the highest OR were C diff. (OR, 11.7 in CD, and OR, 17.9 in UC), followed by cytomegalovirus [CMV](OR, 10.5 in CD, and OR, 14.6 in UC). The remaining OIs are described in Table 1. CMV (OR, 1.28 in CD; P=0.021, and OR, 1.59 in UC) was more prevalent in males than in females in both CD and UC. However, candidiasis (OR, 0.45 in CD, and OR, 0.44 in UC), influenza (OR, 0.81 in CD, and OR 0.84 in UC), human papilloma virus (OR, 0.52 in CD, and OR, 0.46 in UC), and HSV (OR, 0.48 in CD, and OR, 0.46 in UC) were more prevalent in females in both CD and UC. In CD, C diff. (OR, 0.92; P=0.0091) was less prevalent in males, however, in UC there was numerical trend for lower prevalence but it did not reach statistical significance. Pneumocystis, aspergillosis and legionellosis were more prevalent in males with CD but not UC. There was no gender differences in histoplasmosis, cryptococcus, pneumococcal disease, EBV and tuberculosis. All p values <0.0001 unless otherwise stated. Conclusion: In this large population based study we found that OIs are more prevalent in UC and CD as compared to non-IBD controls. We also report that in this large national database, females have a higher prevalence of UC and CD and there is a gender based difference in the prevalence of many OIs.685 Figure 1. Prevalence /100, 000 of Fungal, Bacterial, and Viral OI in CD and UC compared to non IBD control.